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Full-Text Articles in Medicine and Health Sciences
Altered Axon Initial Segment Structure And Function In Inflammatory Disease, Kareem C. Clark
Altered Axon Initial Segment Structure And Function In Inflammatory Disease, Kareem C. Clark
Theses and Dissertations
Axonal pathology is a key contributor to long-term disability in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), but the mechanisms that underlie axonal insults remain unclear. While most axonal pathologies characterized in MS are a direct consequence of myelin loss, we propose that axonal pathologies also occur independent of demyelination. In support of this idea, we recently reported that mice that develop experimental autoimmune encephalomyelitis (EAE), a model commonly used to mimic the pathogenesis of MS, exhibit a structural and functional disruption of the axon initial segment (AIS), a subdomain of the axon that …
Differential Reactivity Of Microglia In Two Mouse Models Of Multiple Sclerosis, Rebecca K. Hartley
Differential Reactivity Of Microglia In Two Mouse Models Of Multiple Sclerosis, Rebecca K. Hartley
Theses and Dissertations
Multiple sclerosis (MS) is a neurodegenerative disorder characterized by CNS inflammation and axonal demyelination. In addition, axonal pathology has also been reported in MS and may be responsible for the functional deficits associated with this disease. Based on preliminary data from our laboratory, we propose that a specific domain of the neuron, known as the axon initial segment (AIS), is targeted in MS. Consistent with our work from the human tissue, we have also observed disruption of AIS integrity in a murine CNS inflammatory model and observations strongly implicate reactive microglia as mediators of AIS disruption. In contrast, a murine …
Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George
Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George
Theses and Dissertations
Axonal domains are required for proper neuron function. These domains are unstable and degenerate concurrent with the inflammation in multiple sclerosis (MS) and the inflammatory disease models experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS) induced inflammation. Previous studies from our laboratory have shown that the axon initial segment (AIS) is maintained independently of the presence of myelin, but that AIS disruption is seen in MS as well as EAE and LPS-mediated inflammation. AIS loss can be interrupted in the early stage of EAE using the anti-inflammatory drug Didox. However, the potential for Didox directed repair of the AIS in later …
The Effect Of Minocycline Treatment On Cell Proliferation And Neurogenesis In The Hippocampus In Young And Aged Brains Following Traumatic Brain Injury, Ashley Harvin
Theses and Dissertations
Following traumatic brain injury, there is an enhanced cell proliferative and neurogenic response in the young adult hippocampus, which may be associated with innate cognitive recovery. However, in the aged brain, an increased level of inflammatory cell responses was observed following injury concomitant to decreased hippocampal neurogenesis and cognitive recovery in the aging population. This suggests that excessive inflammation produced in the injured aging brain has a detrimental effect on neurogenesis and cognitive function. In this study, we examined the effect of anti-inflammatory treatment with minocycline on cell proliferation and generation of new neurons in the dentate gyrus (DG) of …
Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook
Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook
Theses and Dissertations
Mounting evidence indicates an involvement of inflammation in the pathogenesis of Alzheimer’s disease. While there are other mechanisms involved, it is this role of inflammatory processes that we wish to investigate. Triptolide is the major constituent in the Chinese herb, Tripterygium wilfordii Hook F, and has been used for centuries as part of Chinese herbal medicine. The four ringed structure has close homology to drugs of the steroid class and it has been shown to be beneficial as an anti-inflammatory for rheumatoid arthritis and for treatment of certain cancers. The aim of this study was to evaluate the potential therapeutic …
The Role Of Acanthamoeba Culbertsoni Serine Proteases In Abating Microglial-Like Cell Cytokines And Chemokines, Jenica Harrison
The Role Of Acanthamoeba Culbertsoni Serine Proteases In Abating Microglial-Like Cell Cytokines And Chemokines, Jenica Harrison
Theses and Dissertations
Acanthamoeba culbertsoni is an opportunistic free-living amoeba that is causative of granulomatous amoebic encephalitis (GAE), a chronic and often fatal central nervous system (CNS) disease that is most prevalent in immune compromised individuals. One hallmark of this disease is the formation of granulomas within the CNS, which are commonly absent in immune compromised individuals. Granulomas are usually composed of amoebae, microglia (CNS macrophages), macrophages, T cells, B cells, and neutrophils. Previous studies have demonstrated that microglia respond to Acanthamoeba by producing pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF)-α, interleukin (IL)-1α, and IL-1β. In addition, activated microglia and macrophages …
Cannabinoid Modulation Of Chemotaxis Of Macrophages And Macrophage-Like Cells, Erinn Shenee Raborn
Cannabinoid Modulation Of Chemotaxis Of Macrophages And Macrophage-Like Cells, Erinn Shenee Raborn
Theses and Dissertations
Exogenous and endogenous cannabinoids have been reported to modulate functional activities of macrophages. It is recognized that macrophages express primarily the CB2 cannabinoid receptor, but recent studies indicate that its expression is differential in relation to activation state with maximal levels occurring when cells are in "responsive" and "primed" states. The functional activities of macrophages when in these states of activation are the most susceptible to the action of cannabinoids, at least in terms of a functional linkage to the CB2. To assess the effect of cannabinoid treatment on macrophage chemotaxis and test the hypothesis that cannabinoids inhibit the chemotactic …